We have developed novel methods for proteomic study of beta-cells within native islets. Using
antibodies to proinsulin or insulin we reported the first Biosynthetic Interaction Network for insulin
(Pottekat, Cell Reports, 2013). Based upon our finding that many proteins which interact directly with
insulin are T1D GWAS candidates or proteins required for ER homeostasis, we propose to determine
how these proteins and others in their class are altered during progression to T1D. Moreover, based
upon recent evidence of ER stress in T1D islets and our identification of compounds which stabilize
the ER protein folding environment in vivo, we propose to test new strategies for preserving or
restoring beta-cell mass in T1D.